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Dynamics of dual-fluorescent polymersomes with durable integrity in living cancer cells and zebrafish embryos
Biomaterials ( IF 12.8 ) Pub Date : 2018-03-22 , DOI: 10.1016/j.biomaterials.2018.03.037
Sven H.C. Askes , Nelli Bossert , Jeroen Bussmann , Victorio Saez Talens , Michael S. Meijer , Roxanne E. Kieltyka , Alexander Kros , Sylvestre Bonnet , Doris Heinrich

The long-term fate of biomedical nanoparticles after endocytosis is often only sparsely addressed in vitro and in vivo, while this is a crucial parameter to conclude on their utility. In this study, dual-fluorescent polyisobutylene-polyethylene glycol (PiB-PEG) polymersomes were studied for several days in vitro and in vivo. In order to optically track the vesicles' integrity, one fluorescent probe was located in the membrane and the other in the aqueous interior compartment. These non-toxic nanovesicles were quickly endocytosed in living A549 lung carcinoma cells but unusually slowly transported to perinuclear lysosomal compartments, where they remained intact and luminescent for at least 90 h without being exocytosed. Fluorescence-assisted flow cytometry indicated that after endocytosis, the nanovesicles were eventually degraded within 7–11 days. In zebrafish embryos, the polymersomes caused no lethality and were quickly taken up by the endothelial cells, where they remained fully intact for as long as 96 h post-injection. This work represents a novel case-study of the remarkable potential of PiB-PEG polymersomes as an in vivo bio-imaging and slow drug delivery platform.



中文翻译:

具有持久完整性的双荧光聚合物囊泡在活癌细胞和斑马鱼胚胎中的动力学

内吞后的生物医学纳米粒子的长期命运往往只有稀疏解决在体外体内,而这是结束对他们的效用的关键参数。在这项研究中,在体外体内研究了双荧光聚异丁烯-聚乙二醇(PiB-PEG)聚合物囊泡数天。为了光学跟踪囊泡的完整性,一个荧光探针位于膜中,另一个位于水性内部隔室中。这些无毒的纳米囊泡在活的A549肺癌细胞中被快速内吞,但是异常缓慢地被转运到核周的溶酶体区室,在那里它们保持完整且发光至少90小时而没有胞吐。荧光辅助流式细胞仪表明,内吞后,纳米囊泡最终在7-11天内降解。在斑马鱼的胚胎中,聚合物小体没有致死性,并被内皮细胞迅速吸收,在注射后长达96小时内,它们仍保持完整。这项工作代表了PiB-PEG聚合物囊泡在体内的巨大潜力的新颖案例研究 生物成像和缓慢的药物输送平台。

更新日期:2018-03-22
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